Hydrogen Bromide → 21-Bromo-3beta-hydroxypregna-5,16-dien-20-one

HRID 1600583Notes

Reaction equation

HRID 1600583 reaction equation
[CH3:1][C:2]([C:4]1[C@@:8]2([CH3:23])[CH2:9][CH2:10][C@@H:11]3[C@@:16]4([CH3:22])[CH2:17][CH2:18][C@H:19]([OH:21])[CH2:20][C:15]4=[CH:14][CH2:13][C@H:12]3[C@@H:7]2[CH2:6][CH:5]=1)=[O:3].[Br:24]C1(Br)C(=O)NC(=O)NC1=O.Br>O1CCCC1.C(Cl)Cl>[Br:24][CH2:1][C:2](=[O:3])[C:4]1[C@:8]2([CH3:23])[C@H:7]([C@H:12]3[C@H:11]([CH2:10][CH2:9]2)[C@:16]2([CH3:22])[C:15]([CH2:20][C@@H:19]([OH:21])[CH2:18][CH2:17]2)=[CH:14][CH2:13]3)[CH2:6][CH:5]=1

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 9287116-DehydropregnenoloneHCID 948775,5-Dibromobarbituric acid

Product 1

HCID 1064426921-Bromo-3beta-hydroxypregna-5,16-dien-20-oneYield 104.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 16-dehydropregnenolone (5.00 g, 15.90 mmol) and 5,5-dibromobarbituric acid (4.55 g, 15.90 mmol) in tetrahydrofuran (60 mL). Add concentrated aqueous hydrogen bromide (100 μL of a 48% solution) to the stirring solution and heat the reaction at reflux for 1 hour. Cool slightly and then concentrate under vacuum to produce a brown oily foam. Dissolve the residue in methylene chloride (350 mL), rinse with 50% saturated sodium bicarbonate (2×200 mL), brine (125 mL), dry over anhydrous magnesium sulfate, filter and concentrate under vacuum to provide 21-bromo-3β-hydroxypregna-5,16-dien-20-one (6.53 g) as an orange-brown solid, slightly contaminated with starting material. Scheme II, step B; Suspend 21-bromo-3β-hydroxypregna-5,16-dien-20-one (16 mmol) in ethanol (260 mL) and add thiourea (1.33 g, 17.5 mmol). Heat the reaction at reflux for 1 hour and distill off approximately half of the solvent. Allow the reaction to cool to room temperature. Collect the solid by filtration and dry under high vacuum to provide the title compound (3.62 g) as a bright yellow solid. Concentrate the filtrate to approximately 20 mL to provide a second crop, dry under high vacuum and combine with the first crop to provide a total of 4.25 g. Recrystallize this from ethanol to provide the title compound (2.77 g) as a white crystalline solid , mp 258-260° C. (dec); 1H NMR (DMSO-d6) δ 8.85 (broad singlet, 2H), 6.81 (s, 1H), 6.28 (dd, 1H, J=1.9, 3.3 Hz), 5.29 (broad doublet, 1H, J=4.7 hz), 3.43 (q, 2H, J=7.0 Hz), 3.32-3.18 (m, 1H), 1.05 (t, 3H, J=7.0 Hz), 0.99 (s, 3H), 0.94 (s, 3H); 13C NMR (DMSO-d6) δ 169.4, 142.5, 141.6, 135.6, 131.0, 120.1, 102.0, 69.9, 56.4, 55.9, 49.7, 46.1, 42.2, 36.8, 36.2, 34.4, 31.3, 31.2, 30.8, 29.7, 20.4, 19.0, 18.5, 15.8; MS (CI,CH4) m/z (rel. intensity) 371 (MH+, 76), 370 (33), 369 (34), 353 (100), 83 (26), 81 (27).

Workup

  1. temperatureheat
  2. customthe reaction
  3. temperatureat reflux for 1 hour
  4. temperatureCool slightly
  5. concentrationconcentrate under vacuum
  6. customto produce a brown oily foam
  7. washrinse with 50% saturated sodium bicarbonate (2×200 mL), brine (125 mL)
  8. dry with materialdry over anhydrous magnesium sulfate
  9. filtrationfilter
  10. concentrationconcentrate under vacuum

Sources & evidence

ORD record
ord-f7e9d9f5dec045e9893e0c6d316445a0
Source dataset
uspto-grants-1999_11
Patent number
US05977094

Reaction notes

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